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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) of still unclear etiology. In recent years, the search for biomarkers facilitating its diagnosis, prognosis, therapy response, and other parameters has gained increasing attention. In this regard, in a previous meta-analysis comprising 22 studies, we found that MS is associated with higher nitrite/nitrate (NOx) levels in the cerebrospinal fluid (CSF) compared to patients with non-inflammatory other neurological diseases (NIOND). However, many of the included studies did not distinguish between the different clinical subtypes of MS, included pre-treated patients, and inclusion criteria varied. As a follow-up to our meta-analysis, we therefore aimed to analyze the serum and CSF NOx levels in clinically well-defined cohorts of treatment-naïve MS patients compared to patients with somatic symptom disorder. To this end, we analyzed the serum and CSF levels of NOx in 117 patients (71 relapsing–remitting (RR) MS, 16 primary progressive (PP) MS, and 30 somatic symptom disorder). We found that RRMS and PPMS patients had higher serum NOx levels compared to somatic symptom disorder patients. This difference remained significant in the subgroup of MRZ-negative RRMS patients. In conclusion, the measurement of NOx in the serum might indeed be a valuable tool in supporting MS diagnosis. [ABSTRACT FROM AUTHOR]

Although CSF analysis routinely enables the diagnosis of neurological diseases, it is mainly used for the gross distinction between infectious, autoimmune inflammatory, and degenerative disorders of the CNS. To investigate, whether a multi-dimensional cellular blood and CSF characterization can support the diagnosis of clinically similar neurological diseases, we analysed 546 patients with autoimmune neuroinflammatory, degenerative, or vascular conditions in a cross-sectional retrospective study. By combining feature selection with dimensionality reduction and machine learning approaches we identified pan-disease parameters that were altered across all autoimmune neuroinflammatory CNS diseases and differentiated them from other neurological conditions and inter-autoimmunity classifiers that subdifferentiate variants of CNS-directed autoimmunity. Pan-disease as well as diseases-specific changes formed a continuum, reflecting clinical disease evolution. A validation cohort of 231 independent patients confirmed that combining multiple parameters into composite scores can assist the classification of neurological patients. Overall, we showed that the integrated analysis of blood and CSF parameters improves the differential diagnosis of neurological diseases, thereby facilitating early treatment decisions. [ABSTRACT FROM AUTHOR]

While posterior reversible encephalopathy syndrome (PRES) is often characterized by an inflammatory cerebrospinal-fluid (CSF) profile, knowledge of immune cell patterns in PRES is lacking. Thus, we retrospectively characterized CSF and peripheral blood (PB) from 15 PRES patients, which we analyzed by multidimensional flow cytometry (FC). Results were compared to 72 controls, as well as to 9 patients with progressive multifocal leukoencephalopathy (PML, as a relevant differential diagnosis) and 15 multiple sclerosis patients (MS, as a classical neuroinflammatory disorder), respectively. Total protein level in CSF from PRES patients was elevated compared to that in controls, but not to MS and PML. In-depth FC analysis revealed no differences for adaptive immune cells (B cells, plasma cells, CD4+, and CD8+ T cells) in PB or CSF of PRES compared to controls. In contrast, we observed alterations of the adaptive immune response in CSF of PML and MS compared to PRES, indicating that the adaptive immune response is not a driver of disease in PRES. Indeed, PRES was characterized by an innate immune response with CD14++/CD16+ (intermediate) monocytes elevated in PB and CSF, while CD14++/CD16− (classical) monocytes were decreased in PB from PRES patients as compared to controls. Levels of CD14++/CD16+ monocytes correlated with the duration of hospital stay as a surrogate marker for disease severity in PRES patients. Our findings argue for a role of innate rather than adaptive immunity in the pathophysiology of PRES. The observed shift in monocyte subsets might provide valuable diagnostic clues for the clinical management of these patients. [ABSTRACT FROM AUTHOR]